(1) Background: The serum ferritin cut-off to define absolute iron deficiency is not well-established. The aim of the present study was to determine a clinically relevant ferritin threshold by using early serum biomarkers of iron deficiency such as hepcidin and the soluble transferrin receptor; (2) Methods: Two hundred and twenty-eight asymptomatic subjects attending a hospital as outpatients between 1st April 2020 and 27th February 2022 were selected. Iron metabolism parameters as part of the blood analysis were requested by their doctor and included in the study. Then, they were classified into groups according to their ferritin levels and iron-related biomarkers in serum were determined, quantified, and compared between ferritin score groups and anemic subjects. (3) Results: Serum ferritin levels below 50 ng/mL establish the point from which the serum biomarker, the soluble transferrin receptor to hepcidin ratio (sTfR/Hep ratio), begins to correlate significantly with ferritin levels. (4) Conclusion: Ferritin levels ≤ 50 ng/mL are indicative of early iron deficiency; hence, this should be considered as a clinically relevant cut-off for iron deficiency.

Introduction: Severe COVID-19 can result in a significant and irreversible impact on long-term recovery and subsequent immune protection. Understanding the complex immune reactions may be useful for establishing clinically relevant monitoring. Methods: Hospitalized adults with SARS-CoV-2 between March/October 2020 (n = 64) were selected. Cryopreserved peripheral blood mononuclear cells (PBMCs) and plasma samples were obtained at hospitalization (baseline) and 6 months after recovery. Immunological components’ phenotyping and SARS-CoV-2-specific T-cell response were studied in PBMCs by flow cytometry. Up to 25 plasma pro/anti-inflammatory cytokines/chemokines were assessed by LEGENDplex immunoassays. The SARS-CoV-2 group was compared to matched healthy donors. Results: Biochemical altered parameters during infection were normalized at a follow-up time point in the SARS-CoV-2 group. Most of the cytokine/chemokine levels were increased at baseline in the SARS-CoV-2 group. This group showed increased Natural Killer cells (NK) activation and decreased CD16^high NK subset, which normalized six months later. They also presented a higher intermediate and patrolling monocyte proportion at baseline. T cells showed an increased terminally differentiated (TemRA) and effector memory (EM) subsets distribution in the SARS-CoV-2 group at baseline and continued to increase six months later. Interestingly, T-cell activation (CD38) in this group decreased at the follow-up time point, contrary to exhaustion markers (TIM3/PD1). In addition, we observed the highest SARS-CoV-2-specific T-cell magnitude response in TemRA CD4 T-cell and EM CD8 T-cell subsets at the six-months time point. Conclusions: The immunological activation in the SARS-CoV-2 group during hospitalization is reversed at the follow-up time point. However, the marked exhaustion pattern remains over time. This dysregulation could constitute a risk factor for reinfection and the development of other pathologies. Additionally, high SARS-CoV-2-specific T-cells response levels appear to be associated with infection severity.

Resistance and toxicity associated with current treatments for human cytomegalovirus (HCMV) infection highlight the need for alternatives and immunotherapy has emerged as a promising strategy. This study examined the in vitro immunological effects of co-administration of Thymosin-alpha-1 (Tα1) and polyanionic carbosilane dendrimers (PCDs) on peripheral blood mononuclear cells (PBMCs) during HCMV infection. The biocompatibility of PCDs was assessed via MTT and LDH assays. PBMCs were pre-treated with the co-administered compounds and then exposed to HCMV for 48 h. Morphological alterations in PBMCs were observed using optical microscopy and total dendritic cells (tDCs), myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs), along with CD4+/CD8+ T cells and regulatory T cells (Treg), and were characterized using multiparametric flow cytometry. The findings revealed that Tα1 + PCDs treatments increased DC activation and maturation. Furthermore, increased co-receptor expression, intracellular IFNγ production in T cells and elevated Treg functionality and reduced senescence were evident with Tα1 + G2-S24P treatment. Conversely, reduced co-receptor expression, intracellular cytokine production in T cells, lower functionality and higher senescence in Treg were observed with Tα1 + G2S16 treatment. In summary, Tα1 + PCDs treatments demonstrate synergistic effects during early HCMV infection, suggesting their use as an alternative therapeutic for preventing virus infection.

Background: The immunological factors associated with long-term hepatitis C virus (HCV)-specific humoral immunity after cure remain uncharacterized, particularly in people with HIV (PWH). This study investigated T-cell immunophenotypes and plasma biomarkers associated with anti-E2 binding (HCV-E2Abs) and neutralizing antibody (HCV-nAbs) titers 5 years after achieving sustained virologic response (SVR). Methods: This cross-sectional study analyzed 64 PWH with cured HCV and prior advanced fibrosis. We quantified plasma antibody titers against 5 HCV genotypes, T-cell phenotypes (n = 58), and plasma biomarkers (n = 50). Associations were assessed using Generalized Linear Models (gamma distribution, log-link function) adjusted for clinical confounders, reporting adjusted Arithmetic Mean Ratios (aAMRs) and false discovery rate (FDR)-corrected q-values. Results: Higher frequencies of CD4⁺ T-cell activation (CD38⁺; aAMR = 1.58; q = 0.028) and soluble CD27 levels (aAMR = 1.46; q = 0.038) were associated with higher HCV-E2Abs titers. In contrast, memory T-cell activation across CD4⁺ and CD8⁺ compartments (HLA-DR⁺ and CD38+; all q < 0.10) and elevated soluble immune checkpoints (sCD28, sPD-L2, sLAG-3, sCTLA-4; all q < 0.10) were associated with preserved HCV-nAbs titers. Conversely, a higher frequency of naïve CD8⁺ T-cells was associated with lower neutralization capacity (aAMR = 0.41; q = 0.042). Regarding inflammatory markers, soluble TNF-RI was positively associated with neutralizing titers (aAMR = 1.44; q = 0.019), whereas IL-18 was inversely associated (aAMR = 0.53; q = 0.019). Conclusions: Specific activated T-cell subsets, checkpoint shedding, and selective inflammatory signals were associated with higher long-term HCV-nAbs titers in PWH. In contrast, higher frequencies of naïve CD8⁺ T-cells and elevated IL-18 levels were associated with reduced neutralizing capacity.